Afatinib is a 4-anilinoquinazoline compound, chemically known as 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2 buten-1yl]amino}-7-((s)-tetrahydrofuran-3-yloxy) quinazoline:

Afatinib is a tyrosine kinase inhibitor which covalently binds to the kinase domains of EGFR (ErbB1), HER2 (ErbB2), and HER4 (ErbB4) and irreversibly inhibits tyrosine kinase autophosphorylation, resulting in downregulation of ErbB signalling.
Afatinib is approved as its dimaleate salt and is sold under the brand name Gilotrif® in the United States of America and Giotrif® in European countries by Boehringer Ingelheim. It is currently marketed in form of film coated tablets comprising 20, 30, 40 mg and 50 mg (in European countries) Afatinib for oral administration. Afatinib is indicated for the first-line treatment of metastatic non-small cell lung cancer (NSCLC).
The substance Afatinib is disclosed in U.S. RE43,431.
A process for the preparation of Afatinib dimaleate is described in U.S. Pat. No. 8,426,586. The process yields a crystalline polymorph, herein further referred to as “form A”. In U.S. Pat. No. 8,426,586 form A of Afatinib dimaleate is characterized by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC).
According to U.S. Pat. No. 8,426,586 Afatinib dimaleate only exists in one crystalline modification i.e. form A. However, in the meantime further crystalline polymorphs of Afatinib dimaleate have been discovered.
For example crystalline Afatinib dimaleate form C, form D and form E are described in WO 2013/052157.
WO2012/121764 discloses crystalline form B of Afatinib dimaleate and form A, form B, form C and form D of Afatinib free base. Also, some other crystalline salt forms of Afatinib including difumarate, dioxalate, dimesylate, disulfate, di hydrochloride, di succinate salt forms along with some amorphous forms including Afatinib di-L-malate and Afatinib citrate are described.
U.S. Pat. No. 8,545,884 discloses a tablet comprising Afatinib dimaleate prepared by dry granulation via roller compaction. It teaches that an intermediate compaction step is crucial for the tabletting of Afatinib. This process is tedious and requires specific equipment (roller compactor). Also the yield is lower. Thus, there is a need for a more convenient manufacturing process suitable for large scale production which is cost effective and minimises the losses during manufacturing at the same time providing tablets of adequate hardness, proper disintregation time, appropriate dissolution profiles and good storage stability.